Desmoplastic small round cell tumor (DSRCT) is defined genetically by the chimeric fusion of the Ewing's sarcoma and Wilms' tumor genes, generating a novel transcription factor, EWS-WT1. By using cells with inducible EWS-WT1 to screen high-density microarrays, we identified BAIAP3 as a transcriptional target of the chimera. The BAIAP3 promoter is specifically bound in vivo by the (-KTS) isoform of EWS-WT1, consistent with its activation in reporter assays. BAIAP3 encodes a protein implicated in regulated exocytosis, which is colocalized with a secreted growth factor within cytoplasmic organelles. Ectopic expression of BAIAP3 in tumor cells dramatically enhances growth in low serum and colony formation in soft agar. BAIAP3 therefore encodes a transcriptional target of an oncogenic fusion protein that implicates the regulated exocytotic pathway in cancer cell proliferation.
Unlabelled: A novel Hendra virus (HeV) genotype (HeV genotype 2 [HeV-g2]) was recently isolated from a deceased horse, revealing high-sequence conservation and antigenic similarities with the prototypic strain, HeV-g1. As the receptor-binding (G) and fusion (F) glycoproteins of HeV are essential for mediating viral entry, functional characterization of emerging HeV genotypic variants is key to understanding viral entry mechanisms and broader virus-host co-evolution. We first confirmed that HeV-g2 and HeV-g1 glycoproteins share a close phylogenetic relationship, underscoring HeV-g2's relevance to global health.
National and Local Joint Engineering Research Center for Biomanufacturing of Choral Chemicals, Zhejiang University of Technology, Hangzhou, People's Republic of China.
C14-functionalized steroids enabled diverse biological activities in anti-gonadotropin and anticancer therapy. However, access to C14-functionalized steroids was impeded by the deficiency of chemical synthetic methods. Recently, several membrane-bound fungal cytochrome P450s (CYPs) have been identified with steroid C14α-hydroxylation activity.
Extensive research into gene fusions in cancer and other diseases has led to the discovery of novel biomarkers and therapeutic targets. Concurrently, various bioinformatics tools have been developed for fusion detection in RNA sequencing data, which, in the age of increasing affordability of sequencing, have delivered a large-scale identification of transcriptomic abnormalities. Historically, the focus of fusion transcript research was predominantly on coding RNAs and their resultant proteins, often overlooking non-coding RNAs (ncRNAs).
Background: Ewing sarcoma (ES), the second main pediatric bone sarcoma, is characterised by a chromosomal translocation leading to the formation of fusion proteins like EWS::FLI1. While several studies have shown that potassium channels drive the development of many tumours, limited data exist on ES. This work therefore aimed to study the transcriptional regulation of KCNA2 and define the involvement of the Kv1.
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; WIN Consortium, Paris, France; University of Nebraska, Omaha, NE, USA. Electronic address:
Tumor-agnostic US Food and Drug Administration approvals are transforming oncology. They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAF mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms.
